It might be worthwhile to see if there's any way we can use the Gnome modulesets. Alison Lortie did a lot of work on them a couple of years ago to get them to work with one of the BSDs (I forget which), and Darwin is technically a BSD. If that could be made to work it would be more of a work-saver than integrating with Homebrew.
That looked promising. I'm building now using the official modulesets and hitting fewer failures than I expected so far.
Good news! I have coaxed the "meta-gnome-extended-devel-platform" target from the official modulesets to build, start to finish. I needed only about a dozen patches to existing modules, some of which have been committed already.
I'll work on cleaning up my patches to the official modulesets and open a bug in bugzilla for that.
I now have only two modulesets specific to macOS: "sysdeps", containing instructions for building all the stuff from tarballs that vanilla jhbuild has listed as <systemmodule> (such as cairo, itstool, libicu, ...) and "overrides", containing instructions for building stuff that really won't work if you try to build from the vanilla modulesets, currently containing only vala (because the normal moduleset assumes you have a system-installed vala compiler to bootstrap it) and webkit (too many patches, and pinned to 2.10.2.) I'll put this online as soon as I've cleaned up things a bit, probably later today or tomorrow.
How should we integrate this into gtk-osx-build (if at all?) Depending on what the reaction to the bugzilla bug is like, maybe this should go into jhbuild entirely.